Investigators characterize safety profile of belzutifan in advanced RCC

A pooled analysis of 4 clinical trials evaluating the oral HIF-2α inhibitor belzutifan (Welireg) for the treatment of advanced renal cell carcinoma characterized the safety profile of the therapy.¹

The findings were presented at the Society of Urologic Oncology 25th Annual Meeting in Dallas, Texas.

Eric Jonasch, MD

The authors, led by Eric Jonasch, MD, a professor of genitourinary medical oncology at the University of Texas MD Anderson Cancer Center in Houston, included the phase 1 LITESPARK-001 (NCT02974738) study, phase 3 LITESPARK-005 (NCT04195750) study, phase 2 LITESPARK-013 (NCT04489771) study, and phase 2 LITESPARK-004 study (NCT03401788) in their analysis. LITESPARK-001, LITESPARK-005, and LITESPARK-013 evaluated patients with advanced RCC, whereas LITESPARK-004 evaluated patients with von Hippel-Lindau disease–associated RCC.

A total of 576 patients were included in the analysis. All patients had received at least 1 dose of belzutifan 120 mg by mouth QD. Adverse event (AE) severity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 or 5.0. Data cut-off was April 1, 2022 for LITESPARK-001 and LITESPARK-004, June 13, 2023 for LITESPARK-005, and February 10, 2023 for LITESPARK-013.

Median patient age was 61 years (range, 19-90 years). A total of 206 (35.8%) patients were 65 years of age or older. Of the cohort, 441 (76.7%) were male and 135 (23.4%) were female. ECOG Performance Status was 0 in 278 (48.3%) patients, 1 in 288 (50.0%) patients, and 2 in 10 (1.7%) patients. Geographically, 226 (39.2%) of patients were from Western Europe, 221 (38.4%) were from North America, and 129 (22.4%) were from the rest of the world.

Regarding any-cause AEs, AEs of all grades were seen in 572 (99.3%) patients. Grade 3-5 AEs were observed in 355 (61.6%), with serious AEs seen in 236 (41.0%) patients. A total of 288 (50.0%) patients had an AE that led to dose modification, 235 (40.8%) patients had an AE that led to dose interruption, 89 (15.5%) patients had an AE that led to dose reduction, 37 (6.4%) patients had an AE that led to treatment discontinuation, and 19 (3.3%) patients had an AE that led to death.

In terms of treatment-related AEs (TRAEs), TRAEs of all grades were experienced in 526 (91.3%) patients. Grade 3-5 TRAEs were observed in 217 (37.7%) of patients, and in 1 (0.2%) patient, there was a TRAE that led to death.

Anemia was the most frequently observed any-cause AE and was seen in 485 (84.2%) patients. One hundred sixty-six (28.8%) patients had grade 3 or 4 anemia. Median time to onset of first event of any-grade anemia was 29 days. Median time to onset of first event of grade 3 or 4 anemia was 29 days. The median time to resolution of anemia was 70 days.

Anemia was treated with an erythropoiesis-stimulating agent (ESA) only in 111 (22.9%) patients, blood transfusions only in 85 (17.5%) patients, ESA and blood transfusions in 62 (12.8%) patients, and other treatment in 152 (31.3%) patients. Median time to onset of ESA use was 85 days, with a median number of ESA injections per patient of 5. Median duration of ESA use was 196 days. Median time to onset of blood transfusion was 87 days, with a median of 2 transfusions per patient.

Any-grade hypoxia was observed in 94 (16.3%) patients. Grade 3 or 4 hypoxia was seen in 70 (12.2%) patients. Median time to onset of the first event of any-grade hypoxia was 31 days. Median time to onset of the first event of the grade 3 or higher hypoxia was 30 days, and median time to resolution of hypoxia was 11 days. Sixty-six (70.2%) patients were treated with supplemental oxygen therapy. Median time to onset of this therapy was 43 days, with a mediation duration of treatment of 9 days.

REFERENCE

1. Jonasch E, Ghatalia P, de Velasco G, et al. In-depth characterization of the safety profile of belzutifan monotherapy in patients with renal cell carcinoma: a pooled analysis of four clinical trials. Presented at: Society of Urologic Oncology 25th Annual Meeting. December 4-6, 2024. Dallas, Texas. Abstract 47. Accessed December 5, 2024. https://suo-abstracts.secure-platform.com/a/gallery/rounds/21/details/3787